Running head: PROTEIN STRUCTURE: HEMOGLOBIN & MYOGLOBIN 1

Protein Structure: Hemoglobin & Myoglobin

Delia Garcia

GRT-1 Biochemistry

February 16, 2015

Julie Thompson
PROTEIN STRUCTURE: HEMOGLOBIN & MYOGLOBIN 2

Protein Structure: Hemoglobin & Myoglobin

Hemoglobin is a protein found in in red blood cells which is responsible for binding and

transporting oxygen to tissues throughout the body. Myoglobin is a protein which carries oxygen

to muscles throughout the body. The hemoglobin protein consists of four subunits or polypeptide

chains; two of which are alpha subunits and the other two are beta subunits bound in a

quaternary structure. Conversely, Myoglobin consists of a single subunit and has a tertiary

structure.

The subunits of hemoglobin and myoglobin have an affinity for of binding to an oxygen

molecule to the heme group; however myoglobin has the higher affinity of binding to oxygen

because hemoglobin carries oxygen to the myoglobin (Moof University, 2013). The heme group

is found in the center of each subunit. In the center of each heme group an iron atom is found in

both hemoglobin and myoglobin. Moreover, in hemoglobin binding to oxygen molecules is

cooperative, meaning once a single subunit has bonded to oxygen; the remaining subunits have

an increase of desire to bond to oxygen as well.

Hemoglobin Oxygenation vs Deoxygenation

Hemoglobin subsists in three states, the first is deoxygenated and is known as taut (T);

similarly, the second is oxygenated and designated as relaxed (R). Deoxygenated hemoglobin

transforms from the T state to the R state once it binds to oxygen. Furthermore, structural

position of the iron atom in either state is also visible; in the oxygenated state iron atoms become

visibly intersectional (planar) in relation to the heme group (Houghton, Mifflin, Harcourt,

2015). The reaction subsequently tugs on the histidine side chain resulting in protein structural

change. The iron appears to be non-planar when hemoglobin is in the deoxygenated state which

is also attributable to the relationship of the histidine side chain.

PROTEIN STRUCTURE: HEMOGLOBIN & MYOGLOBIN 3

The last property, expressed as the alkaline Bohr effect, also facilitates oxygen loading

in the lungs and unloading in the tissues; the Perutz models of oxygenated and deoxygenated

hemoglobin provide important insights into the structural basis of these three major features of

the equilibria of oxygen with hemoglobin(Ranney & Sharma, Ch. 28, 2011). The Bohr affects

correlates with hemoglobins affinity to bind with oxygen.

The Bohr Effect depicts the shift in oxygen saturation in relation to the pressure of

oxygen. Acidic environments cause hemoglobin to lose the bond with oxygen and increased acid

is equal to a decreased ph. Similarly, an increase in carbon dioxide, increase in temperature

(fever), or an increase in DPG can cause the bonds in hemoglobin to relax and shift the oxygen

disassociation curve to the right (Moof University, 2013). A high ph., lowered temperature,

lower carbon dioxide, and in the presence of fetal hemoglobin causes the bonds in the

hemoglobin to become taught and shifts the dissociation curve to the left.

Sickle Cell Disease

Sickle cell disease is an inherited genetic disorder that turns healthy red blood cells into

abnormal sickle-shaped red blood cells. The mutation which causes sickle cell disease is seen

only in those who have sub-Saharan African descent or ancestry. One letter is changes in the

genetic coding making sickle cell a point mutation which alters a single amino acid within the

hemoglobin. The allele which is found on chromosome 11 shows codominance, which means

homozygous recessive people are the most affected, heterozygous are partially affected and

homozygous dominant are not affected. This allele is common because heterozygous people

carry a natural immunity to malaria through evolutionary natural selection.

This disease in turn can cause various problems within the body such as occlusion in the

blood vessels, swelling of limbs, infarction of tissues, fever, metabolic issues, widespread pain in
PROTEIN STRUCTURE: HEMOGLOBIN & MYOGLOBIN 4

the joints and abdomen along with many more issues (Birdo Studio, 2011). The causal factor

occurs in the mutation of the beta globulin gene located in chromosome 11. During DNA

replication the mutation is first copied by RNA polymerase and the synthesized into mRNA

which encoded with the mutation, and finally in translation, is synthesized by the ribosome into

s globin.

Dimeric s globin then bonds to dimeric globin to form tetrameric /s globins which

bind iron atoms at the hemi group to ultimately form the hemoglobin S molecule. Healthy

hemoglobin, Hemoglobin A has an affinity to bind with oxygen and then carry it to tissues, while

hemoglobin S does not share the same level of affinity. Hemoglobin A also does not bond to

other hemoglobin A proteins because of the oxygenation A; on the other hand, the deoxygenate

hemoglobin S bonds with other hemoglobin S proteins in what is known as polymerization.

Because of the polymerization within the red blood cell, the structure changes to the sickle

shape.

Due to the deoxygenated state of hemoglobin S, free oxygen molecules begin to form

into molecular oxygen as a stable di-radical. Next, free electrons become incorporated into the

oxygen molecule which transforms the oxygen molecule into a superoxide anion (Birdo Studio,

2011). The superoxide anions start to attack the membrane of the red blood cell leaving lesions

along the surface. As such, the superoxide anions begin to attack the hemoglobin S and oxidase

the protein into meta-hemoglobin S. Meta-hemoglobin S begins to attach together to form Heinz

bodies which gather against the membrane. As the Heinz bodies press against the membrane, the

Band 3 protein and phosphatidylserine arrangement is ultimately damaged. Phagocytosis triggers

macrophage response, which devours the sickled cells and produces cytokines that diffuse in the
PROTEIN STRUCTURE: HEMOGLOBIN & MYOGLOBIN 5

central nervous system as a result. With less red blood cells circulating in the body, anemia sets

in (Birdo Studio, 2011).

Diagrams & Models

Model A.1

Diagram A.2.3

Diagram A.4
PROTEIN STRUCTURE: HEMOGLOBIN & MYOGLOBIN 6

Diagram B.1

Diagram B.2
PROTEIN STRUCTURE: HEMOGLOBIN & MYOGLOBIN 7

Diagram B.4-A

Diagram B.4-B
PROTEIN STRUCTURE: HEMOGLOBIN & MYOGLOBIN 8
PROTEIN STRUCTURE: HEMOGLOBIN & MYOGLOBIN 9

Reference

Birdo Studio (2011). Sickle Cell Disease [Video file]. Retrieved from Academiadeciencia

website: https://www.youtube.com/watch?v=R4-c3hUhhyc

Houghton, Mifflin, & Harcourt. (2015). Hemoglobin and Myoglobin. Retrieved from

http://www.cliffsnotes.com/sciences/biology/biochemistry-i/oxygen-binding-by-

myoglobin-and-hemoglobin/hemoglobin-and-myoglobin

Moof University (2013, October 8). Myoglobin and Hemoglobin (Compare and Contrast) [Video

file]. Retrieved from Moof University website: https://www.youtube.com/watch?

v=zbajaSZDl50

Ranney, H.M., & Sharma, V. (2011). Chapter 28: Structure and Function of Hemoglobin .

Williams Hematology. Retrieved from

https://medtextfree.wordpress.com/2011/12/26/chapter-28-structure-and-function-of-

hemoglobin/